Showing papers in "Experimental Physiology in 1991"
TL;DR: The effects of multiple descending volleys on the characteristics of surface EMG responses in hand muscles to magnetic and electrical cortical stimulation (CS) in primates and applications to studies of the motor system in man are described.
Abstract: Historical introduction. Physiology of electrical stimulation of the exposed motor cortex in primates. Transcranial electrical and magnetical stimulation. The effects of multiple descending volleys on the characteristics of surface EMG responses in hand muscles to magnetic and electrical cortical stimulation (CS). Somatotopy. Calculation of central motor conductaion time. Recruitment order of motoneurones. Inhibitory effects from motor CS. Effects of inputs to sensorimotor cortex on the size of muscle responses evoked by CS. Interruption of brain activity by CS. Application to studies of the motor system in man.
681 citations
TL;DR: This review summarizes the rationale of stereology and the most recent developments for estimating the volumes, surface areas, lengths and numbers of structures from the subcellular to the whole organ level.
Abstract: This review summarizes the rationale of stereology and the most recent developments for estimating the volumes, surface areas, lengths and numbers of structures from the subcellular to the whole organ level
264 citations
TL;DR: Both estimates were nevertheless close to those determined by others in the same species for injected proteoglycans and for endogenous hyaluronan calculated from changes in concentration during intravenous infusion of fluid under anaesthesia, suggesting that hyAluronan and proteoglycan are removed from synovial fluid by a common pathway with limited dependence on their molecular dimensions and concentrations.
Abstract: After the injection of [3H]acetyl-labelled hyaluronan into normal rabbit knee joints, about 90% of its isotope content was ultimately accounted for as 3H2O. The rate of elimination of hyaluronan from synovial fluid was therefore estimated from changes in the level of 3H2O in plasma. The half-life of plasma 3H2O was 6.2 days (S.D. 0.7). As estimated from its metabolism to 3H2O, the mean intrasynovial half-life of [3H]hyaluronan of high molecular weight (modal relative molecular mass (Mr) greater than 6.0 x 10(6) was 13.2 h (range 11-15.5 h; n = 4); an otherwise identical preparation of low molecular weight (modal Mr 0.09 x 10(6] exhibited a mean half-life of 10.2 h (range 7.8-13.5 h; n = 4). The difference between the two groups was significant (P = 0.029). Both estimates were nevertheless close to those determined by others in the same species for injected proteoglycans (Mr 2.5 x 10(6), t1/2 = 12 h) and for endogenous hyaluronan calculated from changes in concentration during intravenous infusion of fluid under anaesthesia (t1/2 = 16 h). The similarity suggests that hyaluronan and proteoglycan are removed from synovial fluid by a common pathway with limited dependence on their molecular dimensions and concentrations.
204 citations
TL;DR: Both theory and experiment show that absorption cannot be maintained across most low‐pressure exchange segments due to the finite permeability of microvessels to plasma protein, which leads to a rise in pericapillary interstitial oncotic pressure with time around absorbing microvascular segments.
Abstract: The evidence for the functional importance of extravascular Starling pressures now seems overwhelming, and when these terms are taken into account it is difficult to uphold the traditional conception that upstream microvascular filtration is largely matched by a sustained downstream reabsorption. Transient absorption can occur, however, during spontaneous vasomotion cycles, during sympathetic-induced vasoconstriction and during hypovolaemic hypotension. Sustained absorption is possible in specialized tissues where the interstitium is 'flushed' by an independent stream (intestinal mucosa, renal cortex, lymph nodes). Both theory and experiment show, however, that absorption cannot be maintained across most low-pressure exchange segments due to the finite permeability of microvessels to plasma protein, which leads to a rise in pericapillary interstitial oncotic pressure with time around absorbing microvascular segments. Extravascular hydraulic resistance may be a further determinant of net fluid transfer rate in situations where capillary wall resistance is low.
172 citations
TL;DR: Results from an in vivo luminal perfusion technique are in part consistent with the presence of a Ca‐H exchanger in the apical membrane of the distal colon mediating Ca uptake into the epithelial cell.
Abstract: An in vivo luminal perfusion technique was used to investigate whether short-chain fatty acids influence the absorption of Ca by the rat colon. Na and water absorption were also determined. In the distal colon, acetate and butyrate caused a significant increase in Ca absorption, while the absorption of Na and water were not affected. In the proximal colon, butyrate did not influence Ca absorption, but significantly enhanced Na and water absorption. These results are in part consistent with the presence of a Ca-H exchanger in the apical membrane of the distal colon mediating Ca uptake into the epithelial cell.
148 citations
TL;DR: At least four types of outward current can be distinguished in isolated rabbit pulmonary artery cells, including a novel transient current which could be activated from the resting potential and could therefore be responsible for the inability of large elastic arteries to fire action potentials.
Abstract: Single cells from the rabbit pulmonary artery were isolated using a new and convenient procedure. Strips of muscle were incubated overnight in papain at 6 degrees C and dispersed the following morning after warming the tissue for 10 min. This method consistently produced a high yield of relaxed cells, which reversibly responded to vasoconstrictors and remained viable for many hours. The electrophysiological properties of these cells were studied using the patch-clamp technique in the whole-cell configuration. In physiological Ca2+ solution with K(+)-filled pipettes, cells had a high input resistance (approximately 17 G omega) and an average resting potential of -55 mV. In voltage clamp, several components of outward current could be identified. Depolarizing voltage steps revealed a prominent, transient current (Itran), having extremely rapid activation (less than 5 ms) and inactivation (less than 15 ms) kinetics. Itran was followed by a more slowly activating current (IKso) that was sustained over 100 ms. Both currents were essentially abolished by a 4-aminopyridine (4-AP) and sensitive to Ca2+ influx. IKso, but not Itran, was blocked by tetraethylammonium (TEA) and had the properties of a Ca(2+)-activated K+ current. Holding the membrane potential at -40 mV completely inactivated Itran and unmasked a time-independent, background current superimposed on IKso. The background current was also blocked by 4-AP. In addition, when adenosine triphosphate (ATP), but not guanosine triphosphate (GTP), was omitted from the patch-pipette, spontaneous bursts of outward current (SOCs) were superimposed on the voltage-activated currents. However, since SOCs were rarely observed when ATP and GTP were present together, they are unlikely to be active under physiological conditions. Thus at least four types of outward current can be distinguished in isolated rabbit pulmonary artery cells. These include a novel transient current which could be activated from the resting potential. It activates much more rapidly than outward currents previously reported in vascular muscle, and would rapidly oppose action potential firing. This current could therefore be responsible for the inability of large elastic arteries to fire action potentials.
119 citations
TL;DR: The major part of the hyaluronan injected in the skin was, however, catabolized by lymphatic removal and subsequent degradation in local lymph nodes and liver.
Abstract: The catabolism of hyaluronan has been studied by injecting hyaluronan, labelled with 125I-tyramine cellobiose (125I-TC), subcutaneously into the hindpaw of rabbits. Following endocytosis, 125I-TC remains in the cells at the site of uptake, allowing localization of the site of catabolism. At 6 h after subcutaneous injection, 65% of the injected radioactivity was recovered. The skin at the injection site contained 47%, the popliteal gland at the side of injection 10%, and the liver 8% of the injected dose. At 48 h the three organs contained 40% of the injected dose with 17% in the skin, 10% in the lymph node and 13% in the liver. The decline in recovery could be accounted for by urinary excretion of the tracer, implying that some tracer had been released from the cells after endocytosis. Chromatography revealed that over 85% of 125I-TC-hyaluronan in the lymph nodes and liver was of low molecular mass throughout the experiment. In skin, 4% of the injected tracer was recovered with low molecular mass at 6 h, increasing to 12% of injected dose at 24 and 48 h. Thus, a minimum of 12% of the injected tracer was catabolized per 24 h at the skin injection site. If cells in skin are responsible for the subsequent release of tracer, as seen from the decrease in recovery of the injected dose, another 10-15% of the tracer could have been catabolized locally in the skin per day. The major part of the hyaluronan injected in the skin was, however, catabolized by lymphatic removal and subsequent degradation in local lymph nodes and liver.
96 citations
TL;DR: Electric fields enhance regeneration of damaged PNS and CNS neurones in animals as diverse as lampreys, frogs, rats and guinea‐pigs, but the mechanisms by which fields produce their effects are not understood.
Abstract: The presence of voltage gradients within developing and damaged tissues led to the notion that the resultant electrical fields provide instructional cues to cells. Field effects on avian and amphibian neurones in vitro include increased differentiation, turning of neurites towards the cathode, increased rate of growth towards the cathode, resorption of anodefacing neurites, increased branching and increased filopodial activity. Electric fields enhance regeneration of damaged PNS and CNS neurones in animals as diverse as lampreys, frogs, rats and guinea-pigs, but the mechanisms by which fields produce their effects are not understood. Further examination of the interaction of fields with intracellular elements, such as the cytoskeleton and second messenger systems, may offer some insight.
95 citations
TL;DR: The results presented in this lecture show that anaesthetic agents impede the transfer of information from the periphery to the cerebral cortex as a reduction in the amplitudes of the initial positive and negative waves of the cerebral cortical response evoked by simulation of the periphery and as an increase in the latency of this response.
Abstract: The results presented in this lecture show that anaesthetic agents impede the transfer of information from the periphery to the cerebral cortex. This is shown both as a reduction in the amplitudes of the initial positive and negative waves of the cerebral cortical response evoked by simulation of the periphery and as an increase in the latency of this response. This effect is most probably a prime effect of anaesthesia since (a) it is common to all the anaesthetics used, (b) the potency of the anaesthetics is directly proportional to their lipid solubility, and (c) the effect is reversed by high ambient pressures. The major site at which information transfer is most susceptible to the action of anaesthetics is at the level of the ventrobasal thalamus, although the cells in cortical layer V also appear to have an enhanced susceptibility to anaesthetic action. This latter observation is seen both in whole animal and cortical slice preparations. None the less, the first site of synaptic transfer at which anaesthetics exert a profound effect is upon the monosynaptically generated responses of ventrobasal thalamic neurones to cuneothalamic input. A possible mechanism of action for anaesthetic agents acting at this site would be upon a hypothetical cortico-thalamic-reticular-thalamic loop with the theoretical ability to control the responsiveness of the ventrobasal thalamic cells. This action was proposed both from the activity of neurones in response to anaesthetic agents and the anatomical arrangement seen in the thalamus. The thalamic reticular nucleus is a curved sheath of cells situated between the internal capsule and the external medullary lamina, capping and bounding laterally the specific nuclei of the dorsal thalamus. There is both anatomical and physiological evidence that the thalamic reticular nucleus comprises part of the thalamic reticular formation: its cellular structure also resembles that of the brain stem regions of the reticular formation (Ramon-Moliner, 1975). Early degeneration and Golgi studies showed that ascending fibres from the medial parts of the pontine and mesencephalic components of the brain stem reticular formation innervated the thalamic reticular nucleus ventrally, by penetrating the zona incerta, and dorsally, via the intralaminar and dorsal thalamic nuclei (Scheibel & Scheibel, 1958). These observations have been confirmed and extended more recently and it appears that the major innervation of the thalamic reticular nucleus occurs via the ventral route which follows the entire course of the reticular nucleus. No fibres ascending from the dorsal column lemniscal system, the spino-cervico-lemniscal system or the spinothalamic tract have been observed to terminate within the thalamic reticular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
91 citations
TL;DR: In this article, the authors propose a method to solve the problem of unstructured data in the context of data augmentation, which is based on the concept of self-organization.
Abstract: CONTENTS PAGE
79 citations
TL;DR: Single guinea‐pig ventricular myocytes were loaded with the fluorescent Ca2+ indicator Indo‐1 AM and stretched by carbon fibres and observed that a stretch increased resting [Ca2+]i in seven out of eight cells.
Abstract: Single guinea-pig ventricular myocytes were loaded with the fluorescent Ca2+ indicator Indo-1 AM and stretched by carbon fibres. Stretching increased resting tension. Sarcomere lengths were increased by 2-18%. It was observed that a stretch increased resting [Ca2+]i in seven out of eight cells. The change in [Ca2+]i increased with the size of the stretch and returned to pre-stretch levels on return to resting cell length. These observations suggest a means by which changes in resting muscle length can modify the contractile state of cardiac muscle.
TL;DR: A minor absorption into blood of long‐chain fatty acids compared to the medium‐ Chain fatty acids is confirmed and differences in the catabolism of the fatty acids according to their chain length and their degree of unsaturation are highlighted.
Abstract: Simultaneous portal blood absorption and intestinal mucosal catabolism of labelled fatty acids were investigated. Anaesthetized adult Wistar rats were infused intraduodenally either with 90 mumol of capric (C10:0), oleic (C18:1), linoleic (C18:2) or arachidonic (C20:4) 1–14C acids or with 30 mumol of each labelled fatty acid in addition to 30 mumol of oleic acid and 30 mumol of monopalmitin. For mixed infusates, experiments were carried out with two additional long-chain fatty acids: palmitic (C16:0) and erucic (C22:1) 1–14C acids. Radioactivity was quantified in the lipids and in the catabolic products in portal blood recovered at 5 min intervals for 1 h after infusion. At the end of the experiment, the disappearance of radioactivity from the mucosa was quantified. When labelled fatty acids were infused alone, 49% of the radiolabelled lipid disappearing from the mucosa was recovered in the blood for C10:0, but only 7.8% for C18:1, 6.4% for C18:2 and 10.6% for C20:4. With mixed infusates, 41% of the radiolabelled lipid disappearing from the mucosa was recovered in the blood for C10:0 compared with 12% for C18:1, 10.2% for C18:2, 10.5% for C20:4 and 2.7% for C16:0 and 2% for C22:1. Labelled catabolites appear with the same profiles as those of the respective fatty acids in blood. These studies confirm a minor absorption into blood of long-chain fatty acids compared to the medium-chain fatty acids and highlight differences in the catabolism of the fatty acids according to their chain length and their degree of unsaturation. The differences might be related to the differences in the fatty acid hydrosolubility and to their different affinities for the I- and L-cytosolic fatty acid binding proteins. These phenomena may be important in nutrition in relation to the availability of essential fatty acids.
TL;DR: It is concluded from the latter experiment that the lateral compliance of a cell is greater than its longitudinal compliance, and, therefore, during a twitch contraction, when the cell shortens, the displacement of thecell contents from the two ends of the cell and the expansion of the Cell laterally will not act as a large force to oppose shortening.
Abstract: The length and width of rat and ferret ventricular myocytes have been measured using a linear photodiode array; the volume of the myocytes has been calculated based on the assumption that the cells were elliptical cylinders. During a twitch contraction, there was a decrease in cell length, but no significant change in the calculated cell volume, because the cells increased in width. Inotropic interventions not only resulted in a greater shortening of the cell during each contraction, but also a greater increase in cell width. Changes in cell length, width and volume on changing the osmotic strength of the bathing solution have also been investigated. The increase in volume in hypotonic solution, and the decrease in hypertonic solution, were the result of changes in the cell width; there were no significant changes in the cell length. It is concluded from the latter experiment that the lateral compliance of a cell is greater than its longitudinal compliance, and, therefore, during a twitch contraction, when the cell shortens, the displacement of the cell contents from the two ends of the cell and the expansion of the cell laterally will not act as a large force to oppose shortening.
TL;DR: The ion replacement studies and data from literature suggest that the Na‐H exchange is working in parallel with a Cl‐HCO3 exchange although luminal addition of DIDS did not significantly influence Cl transport.
Abstract: This study was designed to study the mechanism of electroneutral Na and Cl transport across the isolated rumen epithelium of sheep. Net sodium transport (5.75 +/- 0.35 microequiv cm-2 h-1) was significantly higher than the short-circuit current (0.95 +/- 0.08 microequiv cm-2 h-1). Both, net sodium and net chloride transport were markedly reduced by replacement of chloride, bicarbonate and sodium, respectively, but were not changed by the absence of mucosal potassium. Net sodium and net chloride absorption was significantly decreased by 1.0 mM-amiloride. Mucosal addition of bumetanide, furosemide, hydrochlorothiazide or low concentrations of amiloride (less than 0.1 mM) did not change sodium fluxes. These results provide compelling evidence consistent with the presence of Na-H exchange as the predominant electroneutral mechanism for transepithelial sodium movement. The ion replacement studies and data from literature suggest that the Na-H exchange is working in parallel with a Cl-HCO3 exchange although luminal addition of DIDS (4,4'diisothiocyanatostilbene-2,2'-disulphonate, 1 mM) did not significantly influence Cl transport.
TL;DR: The results suggest that the adaptation properties of a mechanoreceptor may be due to the presence of a particular type of ionic channel in the terminals of the nerve which is also present in the membrane of its soma.
Abstract: The electrical properties of the somata of neurones associated with low-threshold, cutaneous mechanoreceptors were studied in young, anaesthetized rats. The adaptation properties of slowly and rapidly adapting afferents were compared by recording from the somata during mechanical stimulation of the skin and during the injection of depolarizing current pulses through the recording electrode. Membrane potential and action potential conformation were recorded from each cell, together with the axonal conduction velocity. Axonal conduction velocities were in the ranges 62-18 m/s (A alpha/beta) and 7-4 m/s (A delta). Somata with A alpha/beta-axons which were associated with slowly adapting receptors gave sustained discharges when depolarized by injected current, whereas those associated with rapidly adapting receptors gave a brief discharge only (median response: five impulses). Somata with A delta-axons had similar characteristics to fast-conducting, rapidly adapting afferents. In a separate study it was shown that, for neurones which gave an adapting response to intracellular current injection, action potentials recorded from the somata were able to follow electrical stimulation of their axons at frequencies up to 100 Hz, indicating that the adaptation of responses to mechanical stimulation in the other experiments was not due to failure of impulses to invade the somata. The results suggest that the adaptation properties of a mechanoreceptor may be due to the presence of a particular type of ionic channel in the terminals of the nerve which is also present in the membrane of its soma.
TL;DR: It was found that resistance to fatigue correlates with succinate dehydrogenase activity and with myofibrillar ATPase activity, and that muscular fatigue is closely related to cellular energetics.
Abstract: This report describes how the resistance to fatigue of a muscle fibre relates to the fibre's most important ATP-producing and ATP-consuming reactions. Twelve intact single muscle fibres were dissected from lumbrical muscles of Xenopus laevis. Their resistance to fatigue induced by repeated tetanic stimulation was determined, as well as their succinate dehydrogenase activity and calcium-stimulated myofibrillar ATPase activity. The enzyme activities were determined by means of quantitative histochemistry. It was found that resistance to fatigue correlates with succinate dehydrogenase activity (r = 0.83) and with myofibrillar ATPase activity (r = -0.74). The highest correlation was found between resistance to fatigue and the ratio of succinate dehydrogenase to myofibrillar ATPase activity (r = 0.93). It is concluded that muscular fatigue is closely related to cellular energetics.
TL;DR: The results suggest that salt‐induced hypertension is associated with impairment of endothelium‐dependent relaxation to histamine but not to ACh, and that histamine‐induced relaxation was significantly attenuated in aortae from salt‐loaded rats.
Abstract: Endothelium-dependent relaxation in response to histamine and ACh has been studied on precontracted aortic rings from control and salt-loaded Sprague-Dawley rats. Both ACh and histamine caused relaxation of the noradrenaline-induced precontraction only in the presence of the endothelium. The relaxation response to ACh in rings from control and salt-loaded rats did not differ significantly whereas histamine-induced relaxation was significantly attenuated in aortae from salt-loaded rats. The results suggest that salt-induced hypertension is associated with impairment of endothelium-dependent relaxation to histamine but not to ACh.
TL;DR: There were significant differences between the two feeding groups in the 24 h profile of maternal plasma osmolality and there was no significant diurnal variation in the plasma concentrations of cortisol in the ewes or fetuses of this group at any stage between 123 and 144 days gestation.
Abstract: The effects of two different feeding regimes on the 24 h profiles of maternal and fetal plasma cortisol and adrenocorticotrophic hormone (ACTH) concentrations were studied in eight pregnant ewes between 123 and 144 days of gestation Once daily-fed ewes (n = 4) received 1 kg of lucerne-chaff at 1100 h, and multi-fed ewes (n = 4) received 100-200 g of lucerne-chaff at 0900, 1100 and 1300 h and then 150 g until 0900 h the following day There were significant differences between the two feeding groups in the 24 h profile of maternal plasma osmolality; once daily feeding at 1100 h was associated with a peak in maternal plasma osmolality at 1500 h whereas maternal plasma osmolality reached plateau levels at around 1700 h in the multi-fed group There were also differences between the two feeding groups in the 24 h profiles of maternal and fetal plasma glucose Maternal and fetal plasma glucose reached peak concentrations at 1900 h in the once daily-fed ewes in contrast to the multi-fed group, where a plateau in maternal and fetal plasma glucose was reached between 1900 h and 0900 h the following day A significant diurnal variation in the plasma concentrations of cortisol was present in the once daily-fed ewes from 123 days gestation and in their fetuses after, but not before, 135 days gestation Plasma cortisol peaked at 1100 h in the ewes and at 1300 h in the fetuses of this group In the once daily-fed group there was also a significant diurnal variation in maternal and fetal plasma ACTH; plasma ACTH concentrations were highest at 1100 h in the ewes aged between 123 and 144 days and in fetuses after 135 days gestation In the multi-fed group, whilst ACTH was highest at 0900 h in the ewes and at 1300 h in the fetuses, there was no significant diurnal variation in the plasma concentrations of cortisol in the ewes or fetuses of this group at any stage between 123 and 144 days gestation
TL;DR: The application of the four main techniques available for examining the properties of alpha‐adrenoceptors, gene coding, radioligand, biochemical and functional methods, has reinforced the earlier subclassification (alpha 1‐ and alpha 2‐subtypes).
Abstract: The application of the four main techniques available for examining the properties of alpha-adrenoceptors, gene coding, radioligand, biochemical and functional methods, has reinforced the earlier subclassification (alpha 1- and alpha 2-subtypes). These different techniques have not yet yielded subclassifications which entirely align when the subtypes have been examined in detail, although a prime reason for this is that the different techniques have not yet all been applied to the same receptors. There is evidence available on each level to indicate that there are further subtypes within the alpha 1- and alpha 2-adrenoceptors as originally defined pharmacologically, with the possible exception of functional evidence at cellular and tissue level for subtypes of alpha 2. The present extension of the subclasses to three each (A,B,C) for alpha 1 and alpha 2 does not withstand cross-examination on every level and seems unlikely to withstand further probing. It remains true that the set of subtypes of alpha-adrenoceptor which can be activated or blocked by drugs in functioning intact tissue preparations and which are shown in Fig. 4 has not been added to by knowledge derived from ligand binding or molecular biology. These techniques have bolstered confidence in the existing functioning categories and have enabled acceleration of drug screening programmes to find new, potent, highly selective antagonists for the known receptors. Rather than taking the categorization of receptors away from the recognition site to the larger molecule, they have reinforced its supremacy. The advantages being gained from the molecular biology of receptors lie in understanding cell signalling and, on the wider genetic scale, on the place of the receptors, among other elements of the cell, in regulation and function within the organism. From the physiologist's point of view, classical pharmacology can still be relied on as the basis for understanding the specificity of drugs which activate or block plasmalemmal receptors and to keep the numbers of these receptors within reason, while molecular biology may increasingly provide the tools to study the subsequent physiological events. A few years ago, one of us commented (in jest!) that the availability of so many different techniques for examining the properties of alpha-adrenoceptors may eventually provide the ultimate answer that there are forty-two subtypes, but that along the way, the original reason for requiring classification might become lost (McGrath, 1983 b).(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: The results showed that both cortex and papilla were sensitive to vasoconstrictor agents, compatible with the suggestion that angiotensin II regulates cortical but not papillary perfusion in the kidney, and that these responses do not depend on prostaglandin, bradykinin, renal perfusion pressure or endothelium‐derived relaxing factor.
Abstract: The effect of angiotensin II on blood pressure and perfusion of blood through the cortex and papilla regions of the kidney was determined in pentobarbitone-anaesthetized rats which were subjected to laser-Doppler flowmetry to estimate regional renal haemodynamics. Angiotensin II was infused at 10, 45 and 150 ng (kg body weight-1 min-1) which caused dose-related increases in blood pressure of 3, 12 and 24%, respectively, and decreases in cortical perfusion of 9, 15 and 24%, respectively. Papillary perfusion did not change at any dose of angiotensin II. This pattern and magnitude of responses to angiotensin II in blood pressure, cortical and papillary perfusions was essentially unaffected (a) following blockade of cyclo-oxygenase activity with indomethacin (1.3 mg kg-1 plus 2 mg kg-1 h-1), (b) during infusion of a bradykinin antagonist, at 1.3 micrograms min-1, (c) when renal perfusion pressure was regulated at control levels and (d) following Methylene Blue administration to inhibit potential endothelial-derived relaxing factor production. By contrast, infusion of phenylephrine at 5, 10 and 20 micrograms kg-1 min-1 caused dose-related increases in blood pressure and decreases in both cortical and papillary perfusions reaching some 28, 7 and 17% respectively at the highest dose of phenylephrine used. These results showed that both cortex and papilla were sensitive to vasoconstrictor agents. They are compatible with the suggestion that angiotensin II regulates cortical but not papillary perfusion in the kidney, and that these responses do not depend on prostaglandin, bradykinin, renal perfusion pressure or endothelium-derived relaxing factor.
TL;DR: There was a nearly twofold range in allantoin excretion (the larger animals excreting less), which implied that the supply of microbial biomass to the host animal per unit of feed ingested could be profoundly affected by feeding level.
Abstract: The recovery in urine of an intrajugular infusion of physiological amounts of allantoin was measured in four sheep nourished by an intragastric infusion of volatile fatty acids and casein (to eliminate rumen fermentation). The recovery was 72% (S.E.M. 7) and the remainder was presumed to have been lost by diffusion into the gut and degradation by gut microflora. Measured in two sheep, allantoin was removed from the blood at a fractional rate of 0.30 h-1, and excreted in urine at 0.23 h-1. Calculation based on creatinine excretion showed glomerular filtration rate and tubular reabsorption of allantoin to be unchanged by the intravenous infusion. Maximal tubular reabsorption at 1.28 mmol day-1 was saturated by the load of endogenous allantoin alone. In a second experiment with seven normally fed sheep (28-50 kg live weight, all given 1 kg feed), urinary excretion and plasma concentration of allantoin were linearly related. However, the errors were such that plasma allantoin concentration would be of little value as a predictor of urinary excretion. There was a nearly twofold range in allantoin excretion (the larger animals excreting less), which implied that the supply of microbial biomass to the host animal per unit of feed ingested could be profoundly affected by feeding level.
TL;DR: A tissue sampling scheme for tandem assessments of whole‐organ physiology and ultrastructure was applied to the lower intestine of White Plymouth Rock hens on low‐ and high‐NaCl diets, and an increase in epithelial cell membrane contributed to, but did not fully explain, the increase in microvillous area.
Abstract: A tissue sampling scheme for tandem assessments of whole-organ physiology and ultrastructure was applied to the lower intestine (coprodaeum) of White Plymouth Rock hens on low- and high-NaCl diets. The objective was to correlate net amiloride-sensitive Na transport determined using the Ussing chamber with the plasma membrane surface areas due to microvilli at the epithelial cell apex. Hens kept on the low-NaCl diet for 3-4 weeks displayed a substantial increase in short-circuit current and in total microvillous membrane surface area. The latter rose from a group mean +/- S.E.M. of about 90 +/- 9.7 cm2 to one of 200 +/- 38 cm2 per organ. An increase in epithelial cell membrane contributed to, but did not fully explain, the increase in microvillous area. No differences in mean cell height or mean cell volume were found but the average cell in the low-NaCl birds was better developed in possessing a greater surface area of microvilli. On the high-NaCl diet, the epithelium was 33 +/- 2.7 microns tall and contained about 270 +/- 15 million cells. Each cell had a volume, on average, of 540 +/- 59 microns 3 and a microvillous surface of 32 +/- 2.6 microns 2. After NaCl depletion, there were 420 +/- 75 million cells and the average microvillous surface was 49 +/- 5.3 microns 2 per cell. The morphological adaptations alone do not explain the increased net Na transport found on the low-NaCl diet. Of cardinal importance is greater density of open Na channels in apical cell membranes.
TL;DR: In sheep the gut appears to play a major role in response to phosphate deprivation, by increasing the capacity to transport phosphate, which is not achieved by increases in the levels of circulating 1,25‐dihydroxycholecalciferol.
Abstract: The transport of phosphate in intestinal brush-border membrane and parotid basolateral membrane vesicles isolated from sheep maintained on high and low phosphate diets have been studied. The mechanism of the transport of phosphate in the intestine is via a proton symporter whilst in the parotid gland it is effected by a Na+ coupled transporter. In sheep fed a low-P diet there is no change in the capacity of the parotid basolateral membrane to transport phosphate into the parotid end piece cells. This is in marked contrast to the response of the enterocyte brush-border membrane, where there is a significant enhancement of the capacity of the membrane to transport phosphate. We conclude that in sheep the gut appears to play a major role in response to phosphate deprivation, by increasing the capacity to transport phosphate. This enhancement is not achieved by increases in the levels of circulating 1,25-dihydroxycholecalciferol.
TL;DR: The time course of the vasopressin response to the central injection of CCK was found to be similar to the period of behavioural inhibition induced when an equivalent dose of the peptide was given by the same route in an earlier feeding experiment.
Abstract: The effects on vasopressin and cortisol secretion of centrally and peripherally administered cholecystokinin octapeptide (CCK) were investigated in conscious prepubertal pigs. Injection of 1.3 micrograms CCK into the lateral cerebral ventricle resulted in a sustained increase in plasma vasopressin after a latency of 5 min but no change in cortisol concentrations. Intravenous injection of 0.7 and 1.3 micrograms/kg CCK initiated a rapid surge (within 2 min) in plasma vasopressin and a later increase in cortisol secretion. The time course of the vasopressin response to the central injection of CCK was found to be similar to the period of behavioural inhibition induced when an equivalent dose of the peptide was given by the same route in an earlier feeding experiment. An analogous situation was also observed when CCK was given peripherally and, in this case, the threshold dose at which the behavioural and endocrine responses were induced was found to be the same.
TL;DR: Results show that muscle tone varies depending on the amount of previous movement or rest and that although neuromuscular stimulation of paralysed muscles increases muscle stiffness and knee resonant frequency, it is in fact restoring such properties of the muscle to a state approaching that of non‐injured controls.
Abstract: Resting muscle tone of the leg was measured in terms of thigh muscle stiffness and knee resonant frequency in muscles of spinal cord injured subjects who had been involved in an electrical neuromuscular stimulation training programme of the thigh muscles over at least 2 months. The thigh circumference of these patients was 6.6% larger than before training commenced (P less than 0.001) and showed increased muscle stiffness and resonant frequency compared to a similar group of paralysed subjects who had not used any neuromuscular stimulation. Resonant frequency and stiffness after the long-term training were similar to those of non-injured controls and therefore the stimulation programme seemed to reverse the effects of paralysis on muscle tone. Short periods of rest (30 min) caused increased muscle stiffness in non-injured controls and paralysed muscles trained by neuromuscular stimulation. Additional 15 min periods of neuromuscular stimulation further increased muscle stiffness in the trained muscles but also in the muscles of paralysed subjects who had no long-term neuromuscular training. In contrast, 15 min sessions of passive movement of the knee decreased muscle stiffness in long-term trained paralysed muscles and untrained paralysed muscles. Knee resonant frequency was also significantly decreased in the trained paralysed muscles. Results show that muscle tone varies depending on the amount of previous movement or rest and that although neuromuscular stimulation of paralysed muscles increases muscle stiffness and knee resonant frequency, it is in fact restoring such properties of the muscle to a state approaching that of non-injured controls.
TL;DR: The presence of circulating antibodies to calcitonin gene‐related peptide (CGRP) enhanced the damaging effect of ethanol on the rat gastric mucosa, suggesting that CGRP released from the peripheral terminals of visceral afferent fibres plays a role in mediating Gastric mucosal defence mechanisms.
Abstract: The presence of circulating antibodies to calcitonin gene-related peptide (CGRP) enhanced the damaging effect of ethanol on the rat gastric mucosa. Taken together with previous experimental and morphological data the results suggest that CGRP released from the peripheral terminals of visceral afferent fibres plays a role in mediating gastric mucosal defence mechanisms.
TL;DR: It is concluded that [K+]O in brain tissue is effectively regulated even when colloidal dye can penetrate the blood‐brain barrier, but excess K+ may have entered the cerebral interstitial space in scattered patches outside the region sensed by the ion‐selective microelectrodes, triggering spreading depression.
Abstract: The blood-brain barrier was breached in urethane anaesthetized rats by infusing hypertonic mannitol or NaCl at high rate under high pressure into one internal carotid artery. Opening of the blood-brain barrier was confirmed by staining of the perfused hemisphere by intravenous Evans Blue dye. Orthodromic-evoked potentials in CA1 region of hippocampus were transiently extinguished, and the extracellular potential in hippocampus and neocortex shifted in the positive direction during hypertonic infusion. After the hypertonic infusion, the permeability of the barrier to K+ was tested by infusing into the internal carotid artery artificial cerebrospinal fluid in which K+ replaced most of the Na+, raising the concentration of K+ in the blood plasma in the superior sagittal sinus to 13-17 mM. Extracellular potential and interstitial potassium concentration ([K+]O) in hippocampus and neocortex, and evoked potentials in hippocampus, remained unchanged during prolonged infusion of high K+, unless and until spreading depression occurred. After a wave of spreading depression, [K+]O returned to baseline in spite of continued high K+ infusion. We conclude that [K+]O in brain tissue is effectively regulated even when colloidal dye can penetrate the blood-brain barrier, but excess K+ may have entered the cerebral interstitial space in scattered patches outside the region sensed by the ion-selective microelectrodes, triggering spreading depression.
TL;DR: In dose‐response experiments at 10 min, CGRP doses of 0.26‐1.04 nmol/100 g body wt were found to give maximal responses, which were well developed in chicks fasted for 22 h but absent in those which were continuously fed, which contrasts with the hypercalcaemic effect of C GRP which is apparent in fed rather than fasted chicks.
Abstract: We have examined the in vivo effects in chicks of intravenously injected chicken (c-) and rat (r-) calcitonin gene-related peptides (CGRP) on uptake into bone of a simultaneously administered 45Ca label. Both peptides caused transient (10 min) increases in 45Ca uptake into a variety of bone types. In dose-response experiments at 10 min, CGRP doses of 0.26-1.04 nmol/100 g body wt were found to give maximal responses. These were well developed in chicks fasted for 22 h but absent in those which were continuously fed. This contrasts with the hypercalcaemic effect of CGRP which is apparent in fed rather than fasted chicks.
TL;DR: Extravascular albumin entry into different regions of brain and optic nerve was insignificant and insensitive to diabetes, except in the hypothalamus and optic nerves where it was raised with increasing duration of diabetes.
Abstract: Diabetes was induced with streptozotocin in rats weighing about 160 g. These were maintained with age-matched controls for up to 14 months, blood glucose being periodically monitored. Half the diabetic and control rats received the aldose reductase inhibitor, Ponalrestat, in their diet. At 3 weeks, 6-7 months and 13-14 months, the vascular permeability in regions of brain, and in optic and sciatic nerves, were measured by maintaining radiotracers in the bloodstream--125I-albumin (100 min), [14C]sucrose (60 min) and 131I-albumin (5 min)--followed by tissue sampling and counting at termination. 131I-albumin estimated residual intravascular plasma. Diabetes of up to 13-14 weeks caused no measurable increase in the sucrose permeability of microvessels in eight different brain regions, in optic or in sciatic nerve. At 3 weeks of diabetes, sucrose permeability in all brain regions and in optic nerve was reduced relative to that in controls. Extravascular albumin entry into different regions of brain and optic nerve was insignificant and insensitive to diabetes, except in the hypothalamus and optic nerves where it was raised with increasing duration of diabetes. In sciatic nerve, extravascular albumin distribution was markedly increased by diabetes, but sucrose permeability was not demonstrably affected. At the level used in the diet, Ponalrestat reduced the sorbitol content of diabetic sciatic nerve but did not protect again the increased permeability to albumin.
TL;DR: Perchlorate is a potent inhibitor of osteoclast function, and acts through an influence on intracellular [Ca2+], and in turn upon the degree of cell retraction, as well as at thiocyanate concentrations that would have produced comparable lyotropic effects as perchlorate.
Abstract: The effects of perchlorate anion (ClO4-) on osteoclast properties were investigated through a number of independent in vivo and in vitro procedures. Intravenous infusion of ClO4- significantly reduced plasma [Ca] in young (50 g) Wistar rats, in the absence of changes in plasma [Mg] or [albumin]. This effect was maximal at 20 min after administration, and at a dose of 600 mumol/rat. Scanning electron-microscope images suggested that the presence of 10 mM-perchlorate reduced both the total area of cortical bone resorbed by freshly disaggregated rat osteoclasts, and the number of osteoclastic excavations in vitro. Similar effects were observed in the presence of 5 mM [Ca2+]. The effects of Ca2+ were potentiated by otherwise ineffective (1 mM) doses of perchlorate. Indo-1 dual-emission microspectrofluorimetry indicated a transient sixfold elevation of cytosolic free [Ca2+], in isolated cultured osteoclasts, with addition of 10 mM-perchlorate. Records of time-lapse video images indicated that this was followed by a marked and sustained cell retraction, by up to 70% of control cell area. Such effects were not observed at thiocyanate concentrations (10 mM) that would have produced comparable lyotropic effects as perchlorate. However, perchlorate did not alter morphometric measures for pseudopodial motility and cell migration. Nor did it influence supernatant concentrations of tartrate-resistant (osteoclastic) acid phosphatase in cultures of resorbing osteoclasts. These findings suggest that perchlorate is a potent inhibitor of osteoclast function, and acts through an influence on intracellular [Ca2+], and in turn upon the degree of cell retraction.